The effect of unfractionated heparin on thrombelastographic analysis in healthy dogs

Objective To determine the effect of single and multiple doses of SQ heparin (200 U/kg) on the thrombelastogram of healthy dogs. Design Prospective study. Setting University research facility. Animals Six random-source female dogs. Interventions Baseline parameters, including a CBC with platelet count, prothrombin time, activated partial thromboplastin time (aPTT), and antithrombin were performed. Thrombelastography (TEG) and aPTT were performed hourly for 12 hours after unfractionated heparin dosing (200 U/kg, SQ). Anti-Xa activity was assayed at 0, 3, 6, and 8 hours. Heparin was then administered every 8 hours for 3 days. The sampling protocol on Day 4 was identical to Day 1. Measurements and Main Results On Day 1, percentage change from baseline for TEG parameter R, as well as absolute values of K, angle, and maximum amplitude (MA) were evaluated. Statistically significant (P < 0.01) prolongation of the R time and a decrease in angle and MA was seen in all dogs by hour 3. R and MA were unmeasurable for most dogs between 3 and 5 hours. All TEG tracings returned to baseline by 12 hours. Day 4 TEG tracings mimicked those on Day 1. Only 1 dog achieved aPTT values outside the reference interval on both days. Anti-Xa activity levels increased on Day 4 but not on Day 1. Based on post hoc in vitro analysis, prolongation of R time occurred at plasma heparin levels as low as 0.075 U/mL, well below the lower limit of detection of the anti-Xa activity level assay. Conclusions Administration of SQ heparin results in progressive changes in the TEG tracing, with maximal change occurring 3-5 hours after dosing. The extensive prolongation of the R time also indicates that TEG may be too sensitive and limits its utility as a monitoring tool for unfractionated heparin therapy.